Few human afflictions are as devastating as diabetes. In all its forms, the chronic disease now affects about 14 million people in the United States. It is the fourth leading cause of death, accounting for the loss of 160,000 lives a year.
Moreover, even those forms of the disease that are not insulin dependent can lead to complications. "Diabetes causes more blindness, kidney failures, and amputations than any other disease in the country," says David M. Nathan, director of diabetes research at Massachusetts General Hospital, Harvard Medical School. "This impact is what makes it so devastating."
The disease results from an insufficient or defective supply of insulin from the pancreas. It results in too much glucose in the blood stream. About 10% of those diagnosed with the disease have insulin-dependent Type I. These individuals need daily insulin injections and are susceptible to secondary complications. It's these patients that are the most likely candidates for treatment with a bioartificial pancreas.
Now under development and testing, these implantable devices would supply the necessary insulin to control glucose levels, while avoiding body rejection and other immunology complications. If successful, they could end the need for onerous daily insulin injections. A key part of that success will involve the use of plastics.
Plastic warriors. Taking advantage of plastics materials and technology, medical researchers have designed and are testing implantable devices that can be inserted into the body to control glucose levels. For insulin-dependent, Type I diabetics, for whom the disease poses major health risks, such devices could end the need for the daily insulin injections.
One such implant, from W.R. Grace's research laboratory, Lexington, MA, has completed extensive tests in animals. It is now poised for human clinical trials. "We hope to get early FDA approval to begin such tests," says Barry A. Solomon, vice president and head of the W.R. Grace research facility. "We're encouraged by the results of tests at the New England Deaconess Hospital on dogs. They showed that the artificial pancreas can effectively control glucose levels for more than six months."
Basically, the implant uses a membrane technology similar to that found in W.R. Grace's hemodialysis device and kidney dialysis machines. It consists of an acrylic housing that contains a coiled membrane surrounded by a chamber filled with porcine pancreatic cells. These islets regulate the amount of insulin produced based on the blood glucose level.
Blood flows through the tubular membrane and is returned to the body's vascular system. The tube contains pores large enough to allow insulin into the blood stream, but small enough to keep unwanted products from contaminating the islets. Surgeons would implant the device, which weighs only 3 oz, under the patient's skin, then graft it to the body's vascular system.
The single, coiled hollow-fiber ultrafiltration membrane consists of a copolymer polyvinyl chloride and polyacrylonitrile (PAN) modified to make it compatible to the application. A medical-grade acrylic serves as the housing.
An epoxy seal within the housing connects each end of the membrane to polytetrafluoro-ethylene (PTFE) vascular graft material. The device, itself, fastens to an artery and a vein. The design includes acrylic seed ports containing silicon injection plugs to replenish and refurbish the active cells. Polyurethane junctions complete the design. Locating the device just under the skin makes it easier to reach the ports with syringes.
Keeping it small. A major concern during our development, says Solomon, was to minimize the size of the device. Such factors as increasing the output of islets and using materials with high-strength-to-weight ratios helped the researchers reach this goal. The materials, he adds, "enabled us to produce a device with thin walls."
Other concerns: making the unit compatible for long-term use and developing the means of inserting new cells without removing the device from the body. Ports that allow cells to be flushed out and new ones inserted address these problems. "We expect cells to last about six months," Solomon says. "The housing should last about three years."
The design required special joints to assure proper sealing. The researchers selected RF welding to join the acrylic housing components. This technique, Solomon explains, eliminated any potential problems that the use of adhesives might have created.
Solomon adds that joining the PTFE vascular graft to the tubular membrane required the development of special tools to form a seamless junction between the membrane and graft.
More help coming. Neocrin Co., Irvine, CA, also has an artificial pancreas under development. The company's efforts center on creating a device with a membrane pouch that will contain purified clusters of animal-derived pancreatic islets. The membranes protect the microencapsulated islets, allowing easy passage of nutrients, glucose, insulin, and waste products. At the same time, the membranes block out larger molecules of the immune rejection system.
Neocrin's goal: "To produce a thin, flexible, biocompatible membrane, yet keep the device as small as possible," says George M. Johnson, executive vice president of product development. Studies conducted with dogs and primates should be completed by year's end. Formal clinical trials are scheduled to begin sometime in 1996.
For the project, Neocrin works with flat membrane sheets that help give the device greater flexibility. The two-layer polymeric membrane features an outer membrane that helps the device preform the needed biochemical exchange and neovascularization. The inner membrane provides immunoprotection of the porcine islets.
"We can assemble our devices in various configurations," says Johnson, "but all will be large enough to hold the required number of encapsulated islets in one unit, allowing for ease of implantation. Still, none will be more than a few square inches in size. And they all will permit access to islet replenishment or withdrawal through a port in the device."
An artificial pancreas design under development at The Polymer Technology Group, Emeryville, CA, employs dense polyurethane membranes.
These are nonporous membranes, explains Robert S. Ward, president of the company. Cast as films or sheets, the membranes are transparent, heat sealable, or solvent bondable, making them easier to fabricate into different shapes. To assemble a unit, two membranes are joined then filled through an injection hole with animal pancreatic cells. The liquid alginate is later jelled to hold the cells apart and assure proper distribution within the artificial device.
The membrane material, says Ward, is basically a hydrophilic, nonporous, segmented copolymer. "We think it has significant advantages over hydrophobic microporous membranes," he adds. "It already has proved effective in animal tests and we expect to start tests involving human patients within the next nine to 24 months."
What's ahead. It may take a while yet before any artificial pancreas completes clinical tests and wins FDA approval. But researchers have little doubt that such implants will prove extremely beneficial for the recipients. Once approved, the first implants will go into the most seriously ill patients.
"Artificial pancreases aim at providing glycemic regulation similar to that of normal pancreatic islets," says W.R. Grace's Solomon. "This same technology could lead to the development of other bioartificial organs."
Experience shows, adds Massachusetts General's Nathan, that treatment of Type I patients must be done in a very pristine, careful way. It requires many injections and many glucose tests by the patients, and is an imperfect way of getting the required insulin. Successful development of an artificial pancreas would make this a far less demanding task.